Investigation of the pharmacokinetics of 3′-deoxy-3′-[18F]fluorothymidine uptake in the bone marrow before and early after initiation of chemoradiation therapy in head and neck cancer

Yusuf Menda, Laura L. Boles Ponto, Kenneth J. Dornfeld, Timothy J. Tewson, G. Leonard Watkins, Anjali K. Gupta, Carryn Anderson, Sarah McGuire, Michael K. Schultz, John J. Sunderland, Michael M. Graham, John M. Buatti

Research output: Contribution to journalArticle

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Abstract

Introduction: The kinetics of the bone marrow uptake of 3'-deoxy-3'-[18F]fluorothymidine (FLT) before and early after initiation of chemoradiation therapy was investigated in patients with head and neck cancer. Methods: Fourteen subjects with head and neck cancer underwent FLT positron emission tomography (PET) at baseline and after 10 Gy of radiation therapy. Thirteen subjects also received one cycle of platinum-based chemotherapy before the second FLT PET. Kinetic parameters, including the flux constant based on compartmental analysis (KFLT) and the Patlak constant (KPatlak) for cervical marrow, were calculated. Standardized uptake values (SUVs) for the cervical marrow (inside the radiation field) and lumbar spine marrow (outside the radiation field) were also determined. Results: There was a significant drop in FLT uptake in the bone marrow inside the radiation field. Mean pretreatment uptake values for the cervical spine were SUV=3.08±0.66, KFLT=0.045±0.016 min-1 and KPatlak=0.039±0.013 min-1. After treatment, these values were SUV=0.74±0.19, KFLT=0.011±0.005 min-1 and KPatlak=0.005±0.002 min-1. Compartmental analysis revealed a significant drop in k3 in irradiated cervical marrow. FLT uptake in the bone marrow outside the radiation field exhibited a significantly smaller decrease. Conclusions: There is a marked decrease in FLT uptake in irradiated bone marrow after 10 Gy of radiation therapy to the head and neck. The drop in FLT uptake in irradiated marrow is due to a significant decrease in the net phosphorylation rate of FLT.

Original languageEnglish (US)
Pages (from-to)433-438
Number of pages6
JournalNuclear Medicine and Biology
Volume37
Issue number4
DOIs
StatePublished - May 1 2010

Fingerprint

Head and Neck Neoplasms
Pharmacokinetics
Bone Marrow
Radiation
Radiation Dosage
Therapeutics
Positron-Emission Tomography
Spine
Radiotherapy
alovudine
Platinum
Neck
Head
Phosphorylation
Drug Therapy

Keywords

  • 3′-Deoxy-3′-[F]fluorothymidine
  • Bone marrow
  • Chemoradiation
  • FLT

ASJC Scopus subject areas

  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

Investigation of the pharmacokinetics of 3′-deoxy-3′-[18F]fluorothymidine uptake in the bone marrow before and early after initiation of chemoradiation therapy in head and neck cancer. / Menda, Yusuf; Boles Ponto, Laura L.; Dornfeld, Kenneth J.; Tewson, Timothy J.; Watkins, G. Leonard; Gupta, Anjali K.; Anderson, Carryn; McGuire, Sarah; Schultz, Michael K.; Sunderland, John J.; Graham, Michael M.; Buatti, John M.

In: Nuclear Medicine and Biology, Vol. 37, No. 4, 01.05.2010, p. 433-438.

Research output: Contribution to journalArticle

Menda, Y, Boles Ponto, LL, Dornfeld, KJ, Tewson, TJ, Watkins, GL, Gupta, AK, Anderson, C, McGuire, S, Schultz, MK, Sunderland, JJ, Graham, MM & Buatti, JM 2010, 'Investigation of the pharmacokinetics of 3′-deoxy-3′-[18F]fluorothymidine uptake in the bone marrow before and early after initiation of chemoradiation therapy in head and neck cancer', Nuclear Medicine and Biology, vol. 37, no. 4, pp. 433-438. https://doi.org/10.1016/j.nucmedbio.2010.02.005
Menda, Yusuf ; Boles Ponto, Laura L. ; Dornfeld, Kenneth J. ; Tewson, Timothy J. ; Watkins, G. Leonard ; Gupta, Anjali K. ; Anderson, Carryn ; McGuire, Sarah ; Schultz, Michael K. ; Sunderland, John J. ; Graham, Michael M. ; Buatti, John M. / Investigation of the pharmacokinetics of 3′-deoxy-3′-[18F]fluorothymidine uptake in the bone marrow before and early after initiation of chemoradiation therapy in head and neck cancer. In: Nuclear Medicine and Biology. 2010 ; Vol. 37, No. 4. pp. 433-438.
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abstract = "Introduction: The kinetics of the bone marrow uptake of 3'-deoxy-3'-[18F]fluorothymidine (FLT) before and early after initiation of chemoradiation therapy was investigated in patients with head and neck cancer. Methods: Fourteen subjects with head and neck cancer underwent FLT positron emission tomography (PET) at baseline and after 10 Gy of radiation therapy. Thirteen subjects also received one cycle of platinum-based chemotherapy before the second FLT PET. Kinetic parameters, including the flux constant based on compartmental analysis (KFLT) and the Patlak constant (KPatlak) for cervical marrow, were calculated. Standardized uptake values (SUVs) for the cervical marrow (inside the radiation field) and lumbar spine marrow (outside the radiation field) were also determined. Results: There was a significant drop in FLT uptake in the bone marrow inside the radiation field. Mean pretreatment uptake values for the cervical spine were SUV=3.08±0.66, KFLT=0.045±0.016 min-1 and KPatlak=0.039±0.013 min-1. After treatment, these values were SUV=0.74±0.19, KFLT=0.011±0.005 min-1 and KPatlak=0.005±0.002 min-1. Compartmental analysis revealed a significant drop in k3 in irradiated cervical marrow. FLT uptake in the bone marrow outside the radiation field exhibited a significantly smaller decrease. Conclusions: There is a marked decrease in FLT uptake in irradiated bone marrow after 10 Gy of radiation therapy to the head and neck. The drop in FLT uptake in irradiated marrow is due to a significant decrease in the net phosphorylation rate of FLT.",
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AU - Boles Ponto, Laura L.

AU - Dornfeld, Kenneth J.

AU - Tewson, Timothy J.

AU - Watkins, G. Leonard

AU - Gupta, Anjali K.

AU - Anderson, Carryn

AU - McGuire, Sarah

AU - Schultz, Michael K.

AU - Sunderland, John J.

AU - Graham, Michael M.

AU - Buatti, John M.

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N2 - Introduction: The kinetics of the bone marrow uptake of 3'-deoxy-3'-[18F]fluorothymidine (FLT) before and early after initiation of chemoradiation therapy was investigated in patients with head and neck cancer. Methods: Fourteen subjects with head and neck cancer underwent FLT positron emission tomography (PET) at baseline and after 10 Gy of radiation therapy. Thirteen subjects also received one cycle of platinum-based chemotherapy before the second FLT PET. Kinetic parameters, including the flux constant based on compartmental analysis (KFLT) and the Patlak constant (KPatlak) for cervical marrow, were calculated. Standardized uptake values (SUVs) for the cervical marrow (inside the radiation field) and lumbar spine marrow (outside the radiation field) were also determined. Results: There was a significant drop in FLT uptake in the bone marrow inside the radiation field. Mean pretreatment uptake values for the cervical spine were SUV=3.08±0.66, KFLT=0.045±0.016 min-1 and KPatlak=0.039±0.013 min-1. After treatment, these values were SUV=0.74±0.19, KFLT=0.011±0.005 min-1 and KPatlak=0.005±0.002 min-1. Compartmental analysis revealed a significant drop in k3 in irradiated cervical marrow. FLT uptake in the bone marrow outside the radiation field exhibited a significantly smaller decrease. Conclusions: There is a marked decrease in FLT uptake in irradiated bone marrow after 10 Gy of radiation therapy to the head and neck. The drop in FLT uptake in irradiated marrow is due to a significant decrease in the net phosphorylation rate of FLT.

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